The Experts below are selected from a list of 163011 Experts worldwide ranked by ideXlab platform
Julio Saezrodriguez - One of the best experts on this subject based on the ideXlab platform.
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signatures of cell death and proliferation in perturbation transcriptomics data from Confounding Factor to effective prediction
Nucleic Acids Research, 2019Co-Authors: Bence Szalai, Vigneshwari Subramanian, Christian H Holland, Robert Alfoldi, Laszlo G Puskas, Julio SaezrodriguezAbstract:Transcriptional perturbation signatures are valuable data sources for functional genomics. Linking perturbation signatures to screenings opens the possibility to model cellular phenotypes from expression data and to identify efficacious drugs. We linked perturbation transcriptomics data from the LINCS-L1000 project with cell viability information upon genetic (Achilles project) and chemical (CTRP screen) perturbations yielding more than 90 000 signature-viability pairs. An integrated analysis showed that the cell viability signature is a major Factor underlying perturbation signatures. The signature is linked to transcription Factors regulating cell death, proliferation and division time. We used the cell viability-signature relationship to predict viability from transcriptomics signatures, and identified and validated compounds that induce cell death in tumor cell lines. We showed that cellular toxicity can lead to unexpected similarity of signatures, Confounding mechanism of action discovery. Consensus compound signatures predicted cell-specific drug sensitivity, even if the signature is not measured in the same cell line, and outperformed conventional drug-specific features. Our results can help in understanding mechanisms behind cell death and removing Confounding Factors of transcriptomic perturbation screens. To interactively browse our results and predict cell viability in new gene expression samples, we developed CEVIChE (CEll VIability Calculator from gene Expression; https://saezlab.shinyapps.io/ceviche/).
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signatures of cell death and proliferation in perturbation transcriptomics data from Confounding Factor to effective prediction
bioRxiv, 2018Co-Authors: Bence Szalai, Vigneshwari Subramanian, Julio SaezrodriguezAbstract:Transcriptomics perturbation signatures are valuable data sources for functional genomic studies. They can be effectively used to identify mechanism of action for new compounds and to infer functional activity of different cellular processes. Linking perturbation signatures to phenotypic studies opens up the possibility to model selected cellular phenotypes from gene expression data and to predict drugs interfering with the phenotype. At the same time, close association of transcriptomics changes with phenotypes can potentially mask the compound specific signatures. By linking perturbation transcriptomics data from the LINCS-L1000 project with cell viability phenotypic information upon genetic (from Achilles project) and chemical (from CTRP screen) perturbations for more than 90,000 signature - cell viability pairs, we show here that a cell death signature is a major Factor behind perturbation signatures. We use this relationship to effectively predict cell viability from transcriptomics signatures, and identify compounds that induce either cell death or proliferation. We also show that cellular toxicity can lead to an unexpected similarity of toxic compound signatures Confounding the mechanism of action discovery. Consensus compound signatures predict cell-specific anti-cancer drug sensitivity, even if the drug signature is not measured in the same cell line. These signatures outperform conventional drug-specific features like nominal target and chemical fingerprints. Our results can help removing Confounding Factors of large scale transcriptomics perturbation screens and show that expression signatures boost prediction of drug sensitivity.
Keld A. Jensen - One of the best experts on this subject based on the ideXlab platform.
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interaction of biologically relevant proteins with zno nanomaterials a Confounding Factor for in vitro toxicity endpoints
Toxicology in Vitro, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Abstract The results of in vitro toxicological studies for manufactured nanomaterials (MNs) are often contradictory and not reproducible. Interference of the MNs with assays has been suggested. However, understanding for which materials and how these artefacts occur remains a major challenge. This study investigated interactions between two well-characterized ZnO MNs (NM-110 and NM-111) and lactate dehydrogenase (LDH), and two interleukins (IL-6 and IL-8). Particles (10 to 640 μg/mL) and proteins were incubated for up to 24 h in routine in vitro assays test conditions. LDH activity (ODLDH), but not interleukins concentrations, decreased sharply in a dose-dependent manner within an hour after exposure (ODLDH
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data supporting the investigation of interaction of biologically relevant proteins with zno nanomaterials a Confounding Factor for in vitro toxicity endpoints
Data in Brief, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Abstract Test materials, like manufactured nanomaterials (MN), may interact with serum proteins, interleukins (IL) and lactate dehydrogenase (LDH) and cause measurement artefacts as a result of e.g., physical adsorption and electrostatic forces, and/or interaction with dissolved species or conditional chemical changes during testing. In this article, data are given on the zeta-potentials of two manufactured ZnO nanomaterials (NM-110 and NM-111) dispersed in 0.05% w/v Bovine Serum Albumin (BSA) water batch dispersions and in Ham's F12 nutrient mixture added Fetal Bovine Serum (FBS), penicillin, and streptomycin and particle free mediums (cHam's F12). Data on the Zeta-potential and the iso-electrical point of lactate hydrogenase in pure Ham's F12 nutrient mixture is also provided. The percentage of added IL-6, IL-8 and LDH remaining after 24-h incubation in cHam's F12 are given as function of MN concentrations. Finally data from thermodynamic chemical reaction modeling of changes in pH and Zn-speciation during dissolution of ZnO or dissolved ZnCl2 additions to Ham's F12 using Geochemist Workbench® are given. For further information, data interpretation and discussion please refer to the research article “Interaction of biologically relevant proteins with ZnO nanomaterials: a Confounding Factor for in vitro toxicity endpoints” (E. Da Silva et al. 2019).
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Data supporting the investigation of interaction of biologically relevant proteins with ZnO nanomaterials: A Confounding Factor for in vitro toxicity endpoints
Elsevier, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Test materials, like manufactured nanomaterials (MN), may interact with serum proteins, interleukins (IL) and lactate dehydrogenase (LDH) and cause measurement artefacts as a result of e.g., physical adsorption and electrostatic forces, and/or interaction with dissolved species or conditional chemical changes during testing. In this article, data are given on the zeta-potentials of two manufactured ZnO nanomaterials (NM-110 and NM-111) dispersed in 0.05% w/v Bovine Serum Albumin (BSA) water batch dispersions and in Ham's F12 nutrient mixture added Fetal Bovine Serum (FBS), penicillin, and streptomycin and particle free mediums (cHam's F12). Data on the Zeta-potential and the iso-electrical point of lactate hydrogenase in pure Ham's F12 nutrient mixture is also provided. The percentage of added IL-6, IL-8 and LDH remaining after 24-h incubation in cHam's F12 are given as function of MN concentrations. Finally data from thermodynamic chemical reaction modeling of changes in pH and Zn-speciation during dissolution of ZnO or dissolved ZnCl2 additions to Ham's F12 using Geochemist Workbench® are given. For further information, data interpretation and discussion please refer to the research article “Interaction of biologically relevant proteins with ZnO nanomaterials: a Confounding Factor for in vitro toxicity endpoints” (E. Da Silva et al. 2019)
Bence Szalai - One of the best experts on this subject based on the ideXlab platform.
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signatures of cell death and proliferation in perturbation transcriptomics data from Confounding Factor to effective prediction
Nucleic Acids Research, 2019Co-Authors: Bence Szalai, Vigneshwari Subramanian, Christian H Holland, Robert Alfoldi, Laszlo G Puskas, Julio SaezrodriguezAbstract:Transcriptional perturbation signatures are valuable data sources for functional genomics. Linking perturbation signatures to screenings opens the possibility to model cellular phenotypes from expression data and to identify efficacious drugs. We linked perturbation transcriptomics data from the LINCS-L1000 project with cell viability information upon genetic (Achilles project) and chemical (CTRP screen) perturbations yielding more than 90 000 signature-viability pairs. An integrated analysis showed that the cell viability signature is a major Factor underlying perturbation signatures. The signature is linked to transcription Factors regulating cell death, proliferation and division time. We used the cell viability-signature relationship to predict viability from transcriptomics signatures, and identified and validated compounds that induce cell death in tumor cell lines. We showed that cellular toxicity can lead to unexpected similarity of signatures, Confounding mechanism of action discovery. Consensus compound signatures predicted cell-specific drug sensitivity, even if the signature is not measured in the same cell line, and outperformed conventional drug-specific features. Our results can help in understanding mechanisms behind cell death and removing Confounding Factors of transcriptomic perturbation screens. To interactively browse our results and predict cell viability in new gene expression samples, we developed CEVIChE (CEll VIability Calculator from gene Expression; https://saezlab.shinyapps.io/ceviche/).
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signatures of cell death and proliferation in perturbation transcriptomics data from Confounding Factor to effective prediction
bioRxiv, 2018Co-Authors: Bence Szalai, Vigneshwari Subramanian, Julio SaezrodriguezAbstract:Transcriptomics perturbation signatures are valuable data sources for functional genomic studies. They can be effectively used to identify mechanism of action for new compounds and to infer functional activity of different cellular processes. Linking perturbation signatures to phenotypic studies opens up the possibility to model selected cellular phenotypes from gene expression data and to predict drugs interfering with the phenotype. At the same time, close association of transcriptomics changes with phenotypes can potentially mask the compound specific signatures. By linking perturbation transcriptomics data from the LINCS-L1000 project with cell viability phenotypic information upon genetic (from Achilles project) and chemical (from CTRP screen) perturbations for more than 90,000 signature - cell viability pairs, we show here that a cell death signature is a major Factor behind perturbation signatures. We use this relationship to effectively predict cell viability from transcriptomics signatures, and identify compounds that induce either cell death or proliferation. We also show that cellular toxicity can lead to an unexpected similarity of toxic compound signatures Confounding the mechanism of action discovery. Consensus compound signatures predict cell-specific anti-cancer drug sensitivity, even if the drug signature is not measured in the same cell line. These signatures outperform conventional drug-specific features like nominal target and chemical fingerprints. Our results can help removing Confounding Factors of large scale transcriptomics perturbation screens and show that expression signatures boost prediction of drug sensitivity.
Emilie Da Silva - One of the best experts on this subject based on the ideXlab platform.
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interaction of biologically relevant proteins with zno nanomaterials a Confounding Factor for in vitro toxicity endpoints
Toxicology in Vitro, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Abstract The results of in vitro toxicological studies for manufactured nanomaterials (MNs) are often contradictory and not reproducible. Interference of the MNs with assays has been suggested. However, understanding for which materials and how these artefacts occur remains a major challenge. This study investigated interactions between two well-characterized ZnO MNs (NM-110 and NM-111) and lactate dehydrogenase (LDH), and two interleukins (IL-6 and IL-8). Particles (10 to 640 μg/mL) and proteins were incubated for up to 24 h in routine in vitro assays test conditions. LDH activity (ODLDH), but not interleukins concentrations, decreased sharply in a dose-dependent manner within an hour after exposure (ODLDH
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data supporting the investigation of interaction of biologically relevant proteins with zno nanomaterials a Confounding Factor for in vitro toxicity endpoints
Data in Brief, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Abstract Test materials, like manufactured nanomaterials (MN), may interact with serum proteins, interleukins (IL) and lactate dehydrogenase (LDH) and cause measurement artefacts as a result of e.g., physical adsorption and electrostatic forces, and/or interaction with dissolved species or conditional chemical changes during testing. In this article, data are given on the zeta-potentials of two manufactured ZnO nanomaterials (NM-110 and NM-111) dispersed in 0.05% w/v Bovine Serum Albumin (BSA) water batch dispersions and in Ham's F12 nutrient mixture added Fetal Bovine Serum (FBS), penicillin, and streptomycin and particle free mediums (cHam's F12). Data on the Zeta-potential and the iso-electrical point of lactate hydrogenase in pure Ham's F12 nutrient mixture is also provided. The percentage of added IL-6, IL-8 and LDH remaining after 24-h incubation in cHam's F12 are given as function of MN concentrations. Finally data from thermodynamic chemical reaction modeling of changes in pH and Zn-speciation during dissolution of ZnO or dissolved ZnCl2 additions to Ham's F12 using Geochemist Workbench® are given. For further information, data interpretation and discussion please refer to the research article “Interaction of biologically relevant proteins with ZnO nanomaterials: a Confounding Factor for in vitro toxicity endpoints” (E. Da Silva et al. 2019).
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Data supporting the investigation of interaction of biologically relevant proteins with ZnO nanomaterials: A Confounding Factor for in vitro toxicity endpoints
Elsevier, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Test materials, like manufactured nanomaterials (MN), may interact with serum proteins, interleukins (IL) and lactate dehydrogenase (LDH) and cause measurement artefacts as a result of e.g., physical adsorption and electrostatic forces, and/or interaction with dissolved species or conditional chemical changes during testing. In this article, data are given on the zeta-potentials of two manufactured ZnO nanomaterials (NM-110 and NM-111) dispersed in 0.05% w/v Bovine Serum Albumin (BSA) water batch dispersions and in Ham's F12 nutrient mixture added Fetal Bovine Serum (FBS), penicillin, and streptomycin and particle free mediums (cHam's F12). Data on the Zeta-potential and the iso-electrical point of lactate hydrogenase in pure Ham's F12 nutrient mixture is also provided. The percentage of added IL-6, IL-8 and LDH remaining after 24-h incubation in cHam's F12 are given as function of MN concentrations. Finally data from thermodynamic chemical reaction modeling of changes in pH and Zn-speciation during dissolution of ZnO or dissolved ZnCl2 additions to Ham's F12 using Geochemist Workbench® are given. For further information, data interpretation and discussion please refer to the research article “Interaction of biologically relevant proteins with ZnO nanomaterials: a Confounding Factor for in vitro toxicity endpoints” (E. Da Silva et al. 2019)
Anders Baun - One of the best experts on this subject based on the ideXlab platform.
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interaction of biologically relevant proteins with zno nanomaterials a Confounding Factor for in vitro toxicity endpoints
Toxicology in Vitro, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Abstract The results of in vitro toxicological studies for manufactured nanomaterials (MNs) are often contradictory and not reproducible. Interference of the MNs with assays has been suggested. However, understanding for which materials and how these artefacts occur remains a major challenge. This study investigated interactions between two well-characterized ZnO MNs (NM-110 and NM-111) and lactate dehydrogenase (LDH), and two interleukins (IL-6 and IL-8). Particles (10 to 640 μg/mL) and proteins were incubated for up to 24 h in routine in vitro assays test conditions. LDH activity (ODLDH), but not interleukins concentrations, decreased sharply in a dose-dependent manner within an hour after exposure (ODLDH
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data supporting the investigation of interaction of biologically relevant proteins with zno nanomaterials a Confounding Factor for in vitro toxicity endpoints
Data in Brief, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Abstract Test materials, like manufactured nanomaterials (MN), may interact with serum proteins, interleukins (IL) and lactate dehydrogenase (LDH) and cause measurement artefacts as a result of e.g., physical adsorption and electrostatic forces, and/or interaction with dissolved species or conditional chemical changes during testing. In this article, data are given on the zeta-potentials of two manufactured ZnO nanomaterials (NM-110 and NM-111) dispersed in 0.05% w/v Bovine Serum Albumin (BSA) water batch dispersions and in Ham's F12 nutrient mixture added Fetal Bovine Serum (FBS), penicillin, and streptomycin and particle free mediums (cHam's F12). Data on the Zeta-potential and the iso-electrical point of lactate hydrogenase in pure Ham's F12 nutrient mixture is also provided. The percentage of added IL-6, IL-8 and LDH remaining after 24-h incubation in cHam's F12 are given as function of MN concentrations. Finally data from thermodynamic chemical reaction modeling of changes in pH and Zn-speciation during dissolution of ZnO or dissolved ZnCl2 additions to Ham's F12 using Geochemist Workbench® are given. For further information, data interpretation and discussion please refer to the research article “Interaction of biologically relevant proteins with ZnO nanomaterials: a Confounding Factor for in vitro toxicity endpoints” (E. Da Silva et al. 2019).
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Data supporting the investigation of interaction of biologically relevant proteins with ZnO nanomaterials: A Confounding Factor for in vitro toxicity endpoints
Elsevier, 2019Co-Authors: Emilie Da Silva, Yahia Kembouche, Ulla Tegner, Anders Baun, Keld A. JensenAbstract:Test materials, like manufactured nanomaterials (MN), may interact with serum proteins, interleukins (IL) and lactate dehydrogenase (LDH) and cause measurement artefacts as a result of e.g., physical adsorption and electrostatic forces, and/or interaction with dissolved species or conditional chemical changes during testing. In this article, data are given on the zeta-potentials of two manufactured ZnO nanomaterials (NM-110 and NM-111) dispersed in 0.05% w/v Bovine Serum Albumin (BSA) water batch dispersions and in Ham's F12 nutrient mixture added Fetal Bovine Serum (FBS), penicillin, and streptomycin and particle free mediums (cHam's F12). Data on the Zeta-potential and the iso-electrical point of lactate hydrogenase in pure Ham's F12 nutrient mixture is also provided. The percentage of added IL-6, IL-8 and LDH remaining after 24-h incubation in cHam's F12 are given as function of MN concentrations. Finally data from thermodynamic chemical reaction modeling of changes in pH and Zn-speciation during dissolution of ZnO or dissolved ZnCl2 additions to Ham's F12 using Geochemist Workbench® are given. For further information, data interpretation and discussion please refer to the research article “Interaction of biologically relevant proteins with ZnO nanomaterials: a Confounding Factor for in vitro toxicity endpoints” (E. Da Silva et al. 2019)
